Inhibitory effect of semaphorin‐3A, a known axon guidance molecule, in the human thymocyte migration induced by CXCL12

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: thymus;    chemotaxis;    CXCR4;    FAK;    ZAP‐;    70;    T cell;   

DOI  :  10.1189/jlb.0111031

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

IntrathymicTcelldifferentiationtakesplacewithinthethymiclobulesanddependsoninteractionsbetweendevelopingthymocytesandcellsofthethymicmicroenvironment.Alongwithdifferentiation,thymocytesmigrateinanorientedprogression,whichistightlyregulatedbyanumberofinteractions,includingonemediatedbythechemokineCXCL12.IthasbeenshownrecentlythatSEMA‐3A,asolublememberofthesemaphorinfamily,isalsoinvolvedinthishumanthymocytemigrationandcanhaveachemorepulsiveandde‐adhesiverole.Herein,westudytheroleofSEMA‐3AontheCXCL12‐drivenmigrationofhumanthymocytes.WehaveshownthatSEMA‐3AisabletoinhibitthechemotaxistriggeredbyCXCL12.SuchaninhibitionwasseeninrespecttoimmatureandmatureCD4/CD8‐definedthymocytesubsetsandcanberevertedspecificallybyneutralizinganti‐SEMA‐3AmAb.WehavealsoshownthatSEMA‐3Aconsistentlydown‐regulatesCXCR4membraneexpressioninallCD4/CD8‐definedthymocytesubsets,andthisdown‐regulationisaccompaniedbyadecreaseinthephosphorylationofFAKandZAP‐70proteinkinases.Takentogether,theseresultsdemonstratetheinvolvementofSEMA‐3AintheregulationofCXCL12‐drivenhumanthymocytemigration,whereitactsasaphysiologicalantagonist...

【 授权许可】

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